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1.
J Am Chem Soc ; 145(20): 10991-10997, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37186951

RESUMO

Herein we disclose a strategy to promote the hydrocarboxylation of unactivated alkenes using photochemical activation of formate salts. We illustrate that an alternative initiation mechanism circumvents the limitations of prior approaches and enables hydrocarboxylation of this challenging substrate class. Specifically, we found that accessing the requisite thiyl radical initiator without an exogenous chromophore eliminates major byproducts that have plagued attempts to exploit similar reactivity for unactivated alkene substrates. This redox-neutral method is technically simple to execute and effective across a broad range of alkene substrates. Feedstock alkenes, such as ethylene, are hydrocarboxylated at ambient temperature and pressure. A series of radical cyclization experiments indicate how the reactivity described in this report can be diverted by more complex radical processes.

2.
Angew Chem Int Ed Engl ; 62(10): e202217653, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631427

RESUMO

The development of high mobility emissive organic semiconductors is of great significance for the fabrication of miniaturized optoelectronic devices, such as organic light emitting transistors. However, great challenge exists in designing key materials, especially those who integrates triplet exciton utilization ability. Herein, dinaphthylanthracene diimides (DNADIs), with 2,6-extended anthracene donor, and 3'- or 4'-substituted naphthalene monoimide acceptors were designed and synthesized. By introducing acceptor-donor-acceptor structure, both materials show high electron mobility. Moreover, by fine-tuning of substitution sites, good integration with high solid state photoluminescence quantum yield of 26 %, high electron mobility of 0.02 cm2  V-1 s-1 , and the feature of hot-exciton induced delayed fluorescence were obtained in 4'-DNADI. This work opens a new avenue for developing high electron mobility emissive organic semiconductors with efficient utilization of triplet excitons.

4.
Open Res Eur ; 2: 106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37982077

RESUMO

Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.

5.
Eur J Med Res ; 26(1): 131, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775981

RESUMO

BACKGROUND: Mucormycosis is a rare fungal infection occurring chiefly in the lung or the rhino-orbital-cerebral compartment, particularly in patients with immunodeficiency or diabetes mellitus. Among Mucorales fungi, Rhizopus spp. are the most common cause of mucormycosis. CASE PRESENTATION: We report a case of pulmonary mucormycosis caused by Rhizopus microsporus in a young patient with diabetes but no other apparent risk factors. The diagnosis mainly relied on clinical manifestation, positive pulmonary tissue biopsy, and fungal culture. The patient was successfully treated with posaconazole oral suspension and remains asymptomatic at one-year follow-up. CONCLUSIONS: Pulmonary mucormycosis is a life-threatening condition and posaconazole is an effective treatment for pulmonary mucormycosis caused by Rhizopus microspores.


Assuntos
Pneumopatias/tratamento farmacológico , Pulmão/efeitos dos fármacos , Mucormicose/tratamento farmacológico , Rhizopus/efeitos dos fármacos , Triazóis/uso terapêutico , Adulto , Antifúngicos/uso terapêutico , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias/microbiologia , Masculino , Mucormicose/microbiologia , Rhizopus/fisiologia , Resultado do Tratamento
6.
Zhonghua Yi Xue Za Zhi ; 101(31): 2448-2453, 2021 Aug 17.
Artigo em Chinês | MEDLINE | ID: mdl-34399558

RESUMO

Objective: To investigate the diagnostic value of serum lipoprotein associated phospholipase A2 (Lp-PLA2), amyloid A (SAA) and immunoglobulin E (IgE) in patients with type 2 diabetes (T2DM) mellitus complicated with atherosclerotic disease. Methods: From June to December 2019, 224 patients with T2DM in the Second Hospital of Lanzhou University were selected, including 144 males and 80 females, aged (61±11) years. According to the results of imaging examination, the patients were divided into T2DM with AS group (T2DM-AS group, n=160) and T2DM group (n=64); Healthy subjects in the same period were selected as healthy control group (n=160). Lp-PLA2, IgE, SAA, hs-CRP, TC, TG, HDL-C, LDL-C and Hcy were detected in all patients and healthy controls. The correlation between the above indexes, gender, age and T2DM with AS was analyzed; Multivariate logistic regression was used to analyze the risk factors of T2DM with AS. Results: Compared with the healthy control group, the levels of IgE and Lp-PLA2 in T2DM-AS group and T2DM group were increased, and the levels of SAA in T2DM-AS group were increased (all P<0.05); Compared with T2DM group, the levels of Lp-PLA2, IgE and SAA were increased in T2DM-AS group (all P<0.05). T2DM with AS was positively correlated with age, IgE, Lp-PLA2 and SAA (r=0.468, 0.269, 0.486, 0.418, all P<0.05), and negatively correlated with HDL-C (r=-0.338, P<0.05). Multivariate logistic regression analysis showed that age (OR=0.865, 95%CI: 0.763-0.982, P<0.05), IgE (OR=0.910, 95%CI: 0.840-0.987, P<0.05) and Lp-PLA2 (OR=0.942, 95%CI: 0.910-0.986, P<0.05) were risk factors of T2DM with AS. ROC curve showed that the combined detection of Lp-PLA2, SAA and IgE could improve the diagnostic efficiency of T2DM with AS (AUC=0.895, P<0.05), the sensitivity was 80.0%, and the specificity was 93.7%. Conclusion: The levels of Lp-PLA2, IgE and SAA increase in T2DM patients with AS. The combined detection of Lp-PLA2, SAA and IgE can improve the diagnostic efficiency of T2DM patients with AS.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , 1-Alquil-2-acetilglicerofosfocolina Esterase , Aterosclerose/diagnóstico , Biomarcadores , Proteína C-Reativa , Pré-Escolar , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Fatores de Risco
7.
Zhonghua Yi Xue Za Zhi ; 101(20): 1518-1522, 2021 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-34044520

RESUMO

Objective: To investigate the changes of interleukin-35 (IL-35) level and CD14+monocytes function in patients with chronic heart failure (CHF). Methods: A total of 74 patients with CHF who were hospitalized in the Department of Cardiology of the First Affiliated Hospital of Zhengzhou University between July 2018 and June 2019 as well as 29 healthy controls (HC) were continuously enrolled. 20 ml fasting anticoagulant peripheral blood was collected in the morning, and plasma was separated. IL-35 level was measured by ELISA. Peripheral CD14+monocytes were purified, and the IL-35 receptor subunits (IL-12Rß2 and gp130 mRNA) relative levels were semi-quantified by real-time PCR. CD14+monocytes were stimulated with IL-35, and were cultured in direct contact or indirect contact with human umbilical vein endothelial cells (HUVEC). Cytokines and granzyme B secretion in the supernatants was measured by ELISA. The percentage of HUVEC death was calculated by measuring lactate dehydrogenase level. The difference of the above indicators were compared between the CHF group and the HC group. Results: The age for the CHF group was (59.4±12.1) years, and 58.1% (43 cases) of them were males. The age for the HC group was (53.9±9.8) years, and 65.5% (19 cases) of them were males. The plasma IL-35 level was higher in the CHF group than the HC group ((22.89±7.58) mg/L vs (16.42±5.47) mg/L, P<0.001). The gp130 mRNA relative level was also higher in the CHF group than the HC group (1.07±0.19 vs 0.98±0.15, P=0.022). CD14+monocytes induced HUVEC death in the CHF group was lower in both direct contact and indirect contact culture system than the HC group (both P<0.001). The granzyme B secretion was also lower in the CHF group than the HC group (P<0.001). The CD14+monocytes induced HUVEC death was down-regulated in response to granzyme B inhibition (P=0.011). Both the CD14+monocytes induced HUVEC death and the granzyme B secretion were reduced in response to IL-35 stimulation (both P<0.001). Conclusion: CHF patients have the elevated IL-35 expression. IL-35 induces CD14+monocytes dysfunction via the inhibition of granzyme B secretion. This process promoted the progression of heart failure.


Assuntos
Insuficiência Cardíaca , Monócitos , Adulto , Idoso , Citocinas , Células Endoteliais , Feminino , Humanos , Interleucinas , Masculino , Pessoa de Meia-Idade
8.
SAR QSAR Environ Res ; 32(5): 379-393, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33823697

RESUMO

Linear and nonlinear quantitative structure-property relationship (QSPR) models were developed based on a dataset with 65 polymer-solvent combinations. Seven quantum chemical descriptors, dipole moment, hardness, chemical potential, electrophilicity index, total energy, HOMO and LUMO orbital energies, were calculated with density functional theory at the B3LYP/6-31 G(d) level for polymers and solvents. Considering the strong correlation between intrinsic viscosity and weight, size, shape as well as topological structure of polymers and solvents, topological descriptors were also applied in this work. Meanwhile, the most appropriate polymer structure representation was investigated by considering 1-5 monomeric repeating units. The molecular descriptors were first screened by using the genetic algorithms-multiple linear regression (GA-MLR), with coefficient of determinations (r2) of 0.78 and 0.83 for the training set and the prediction set, respectively. The support vector machine model (SVM) model based on the selected descriptors subset showed a r2 value of 0.95 for the training set and 0.93 for the prediction set. All statistical results suggest that the established QSPR models have good predictability. Furthermore, a new test set obtained from the literature was used for further validation. The r2 values were 0.81 for the MLR model and 0.90 for the SVM model.


Assuntos
Polímeros/química , Solventes/química , Viscosidade , Teoria da Densidade Funcional , Modelos Lineares , Dinâmica não Linear , Relação Quantitativa Estrutura-Atividade , Máquina de Vetores de Suporte
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(6): 1102-1106, 2020 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-33331321

RESUMO

OBJECTIVE: To evaluate the surgical technique and clinical effect of less invasive intrame-dullary nail fixation combined with titanium cable cerclage in the treatment of subtrochanteric fractures. METHODS: A retrospective study was performed in 46 cases of subtrochanteric fractures in Peking University People's Hospital from January 2015 to December 2017. Among them, there were 14 males and 32 females, with an average age of (77.83±10.66) years (44-92 years); 17 cases on the left side and 29 cases on the right side. The causes of injury included crash from a height, traffic accident and accidental fall. According to Seinsheimer classification, there were 26 cases of type Ⅱ, 11 cases of type Ⅲ, 9 cases of type Ⅳ, and these cases were all closed injury. After admission, these patients underwent continuous tibial tuberosity bone traction to maintain the length and force line of the lower extremity, so as to reduce the difficulty of intraoperative fracture reduction. Anticoagulant therapy was given before operation to reduce perioperative thrombotic complications. All the patients were treated with less invasive intramedullary nail fixation combined with titanium cable cerclage. Operation time, blood loss during surgery, time of fracture healing were recorded, Harris and Sanders scoring system were used to assess hip function after operation at each follow-up time point. RESULTS: All the included patients underwent surgery successfully. Average operative time and intraoperative blood loss of these patients were (131.09 ± 20.06) min and (191.96±111.03) mL, respectively. All the patients were followed up satisfactorily, with an average follow-up time of 28 months. The fractures received bone healing within 3-6 months, average hospital stay was (10.61±2.85) days. The Sanders score was excellent in 3 cases, good in 37 cases and common in 6 cases, with an excellent and good rate of 86.96%. The Harris score was excellent in 6 cases, good in 36 cases, with an excellent and good rate of 91.30%. There were no cases of wound infection, loss of reduction, nonunion of fracture or internal fixation failure. Hip pain symptoms were effectively relieved in most patients. CONCLUSION: Less invasive intramedullary nail fixation combined with titanium cable cerclage can obtain good alignment and stability of fracture ends, which is an effective method for the treatment of subtrochanteric fractures.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Idoso de 80 Anos ou mais , Pinos Ortopédicos , Feminino , Consolidação da Fratura , Fraturas do Quadril/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Titânio , Resultado do Tratamento
11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 870-874, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047721

RESUMO

OBJECTIVE: To investigate the clinical effect of a modified arthroscopic outside-in suture technique in the treatment of meniscus tear using a spinal needle. METHODS: From January 2015 to October 2017, 95 patients treated with this method were followed-up. Among these cases, there were 36 males and 59 females. The age of the patients ranged from 16 to 77 years, (46.79±18.07) years in average. Among them, there were 28 patieats aged 16-35, 53 patients aged 36-65, and 14 patients aged over 65 years old. 28 cases were diagnosed with medial meniscus tear, 43 cases with lateral meniscus tear and 24 cases with both medial and lateral meniscus tear. Causes of the injury included sports, sprain, etc. According to Barrett standard, the clinical healing of meniscus tear was judged. Lysholm score, knee range of motion, visual simulation score (VAS) and magnetic resonance imaging (MRI) were used to evaluate the postoperative knee function and recovery of the patients. RESULTS: The 95 patients were followed up for 22 to 36 months, with an average of (28.32±3.98) months. According to Barrett standard, 90 patients (94.7%) obtained meniscus clinical healing. Meniscal healing rates were 96.43%, 96.23% and 85.71% in the three age groups, respectively. The meniscal healing rate was lower in the elderly group, but there was no significant difference in statistical results (P=0.262). Five patients had deep tenderness in the joint space of the injured side, and the overstretch test was positive. The preoperative and postoperative VAS scores, Lysholm scores and knee motion were compared in each group, and the differences were statistically significant (P < 0.01). At the end of the last follow-up, there were no cases of knee joint effusion, swelling and interlocking, and the joint function was effectively improved in most patients. No surgical site infection, periarticular vascular/nerve injury or knotting reaction was found during the follow-up. CONCLUSION: This modified arthroscopic outside-in suture technique using a spinal needle has the characteristics of simple operation, small trauma and rapid recovery, and the mid-term follow-up results were satisfactory. Therefore, we consider this method to be a safe and efficient method for the treatment of meniscus anterior horn and body tear.


Assuntos
Traumatismos do Joelho , Lesões do Menisco Tibial , Idoso , Artroscopia , Feminino , Seguimentos , Humanos , Traumatismos do Joelho/cirurgia , Masculino , Punções , Técnicas de Sutura , Lesões do Menisco Tibial/cirurgia
12.
Zhonghua Yi Xue Za Zhi ; 100(17): 1315-1319, 2020 May 05.
Artigo em Chinês | MEDLINE | ID: mdl-32375439

RESUMO

Objective: To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in patients with chronic heart failure and its modulatory activity on T lymphocytes. Methods: Eighty-six patients with chronic heart failure (CHF group) who were hospitalized in Department of Cardiology, the First Affiliated Hospital of Zhengzhou University between January and October 2018 were enrolled in the study. Meanwhile, thirty-two healthy controls (HC group) who received healthy examination were also selected. Peripheral blood mononuclear cells were isolated, and TIM-3 expression of CD4(+)and CD8(+)T cells was investigated by flow cytometry. CD4(+)and CD8(+)T cells were purified, and were stimulated by anti-TIM-3 antibody. Interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, IL-35, IL-17, and IL-22 expressions in the supernatants of cultured CD4(+)T cells and tumor necrosis factor-α (TNF-α) and IFN-γ expressions in the supernatants of cultured CD8(+) T cells were measured by enzyme-linked immunosorbent assay. mRNA expressions of T-bet, GATA-3, FoxP3, and RORγt in CD4(+)T cells and perforin and granzyme B in CD8(+)T cells were semi-quantified by real-time PCR. Student t test or paired t test was used for comparisons between the two groups. Results: TIM-3(+) CD4(+) T cell percentage significantly increased in CHF group than that of HC group (3.47%±1.06% vs 0.92%±0.27%, P<0.001). TIM-3(+)CD8(+)T cell percentage also notably elevated in CHF group compared to HC group (6.12%±1.91% vs 1.77%±0.63%, P<0.001). CD4(+)T and CD8(+)T cells were dysfunctional in chronic heart failure. The levels of IFN-γ, IL-17, and IL-22 secreted by purified CD4(+) T cells significantly reduced in CHF group, while IL-10 and IL-35 expressions elevated in CHF group (all P<0.05). The relative mRNA expression levels of T-bet and RORγt in CD4(+) T cells remarkably decreased in CHF group than those of HC group (all P<0.01), while relative expression level of FoxP3 mRNA increased in CHF group (1.93±0.88 vs 0.97±0.28, P=0.031). The levels of TNF-α and IFN-γ produced by purified CD8(+)T cells notably reduced in CHF group than those of HC group (all P<0.05), and relative mRNA expression levels of perforin and granzyme B also decreased in CHF group (all P<0.05). The levels of anti-TIM-3 antibody stimulation-produced IFN-γ, IL-17, and IL-22 increased (all P<0.05) but IL-35 secretion reduced [(61±13) ng/ml vs (72±17) ng/ml, P=0.029] by CD4(+)T cells in CHF group. The relative mRNA expression levels of T-bet and RORγt also elevated in response to anti-TIM-3 antibody stimulation (all P<0.05). Anti-TIM-3 antibody stimulation promoted TNF-α and IFN-γ production by CD8(+)T cells in CHF group (all P<0.01). The relative mRNA expression levels of perforin and granzyme B also increased (all P<0.05). Conclusion: TIM-3 was increasingly expressed in T cells from patients with chronic heart failure, and might take part in the regulation of T cell dysfunction in chronic heart failure.


Assuntos
Insuficiência Cardíaca , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Doença Crônica , Humanos , Imunoglobulinas , Leucócitos Mononucleares , Mucina-3
13.
Eur Rev Med Pharmacol Sci ; 24(2): 591-603, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32016960

RESUMO

OBJECTIVE: Ovarian cancer (OC) is a common tumor in women, and the development of chemoresistance is the major obstacle to its treatment. Long non-coding RNAs (LncRNAs) have been linked to chemoresistance in many cancers. However, the function of lncRNA urothelial carcinoma associated1 (UCA1) in paclitaxel (PTX) resistance of OC is not well elucidated. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UCA1, microRNA-654-5p (miR-654-5p) and salt inducible kinase 2 (SIK2). Cell PTX resistance and proliferation were evaluated by 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The abilities of apoptosis, migration and invasion were measured by Flow cytometry and Transwell assays, respectively. Dual-luciferase reporter assay was used to verify the interaction among UCA1, miR-654-5p and SIK2. Besides, Western blot analysis was performed to assess the protein level of SIK2. RESULTS: UCA1 was markedly upregulated in OC tissues and PTX-resistant OC cells. Silencing of UCA1 restrained the PTX resistance, reduced the proliferation, migration, invasion and enhanced the apoptosis of PTX-resistant OC cells. MiR-654-5p could be sponged by UCA1, and the inhibitory effect of its overexpression on the progression of PTX-resistant OC cells could be reversed by overexpressed-UCA1. Moreover, SIK2 was a target of miR-654-5p. Silencing of SIK2 could hinder the PTX resistance and suppress the progression of PTX-resistant OC cells, while miR-654-5p inhibitor could invert this inhibitory effect. Also, the expression of SIK2 was regulated by miR-654-5p and UCA1 expression. CONCLUSIONS: LncRNA UCA1 plays an active role in PTX resistance of OC and is crucial to maintain the development of PTX resistance in OC, which provides a new therapeutic target for the study of OC chemoresistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MicroRNAs/biossíntese , Neoplasias Ovarianas/metabolismo , Paclitaxel/uso terapêutico , Proteínas Serina-Treonina Quinases/biossíntese , RNA Longo não Codificante/biossíntese , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Células Cultivadas , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , MicroRNAs/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores
14.
Clin Radiol ; 75(1): 70-75, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629485

RESUMO

AIM: To determine the cut-off value of the area ratio under the curve (ARUC) for predicting symptoms of stroke. MATERIALS AND METHODS: Contrast-enhanced ultrasound was used to analyse intraplaque neovascularization (IPN). The correlations between the ARUC and risk factors of stroke were examined. A receiver operating characteristic curve was used to determine the cut-off value of the ARUC. RESULTS: Using a quantitative analysis method for IPN, the ARUC was significantly higher in the symptomatic group than in the asymptomatic group (p=0.017). The ARUC was positively associated with the homocysteine level (r=0.429, p=0.002) and high-sensitivity C-reactive protein level (r=0.424, p=0.003). Regression analysis showed that the ARUC was a risk factor for symptoms of stroke. The receiver operating characteristic curve showed that the cut-off value for symptoms was 0.24; the sensitivity was 77%, and the specificity was 70%; the positive predictive value was 68%, and the negative predictive value was 78%. CONCLUSION: IPN was a risk factor for the occurrence of the clinical symptoms of stroke. Patients with an ARUC of >0.24 had a higher risk of stroke.


Assuntos
Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Neovascularização Patológica/complicações , Neovascularização Patológica/diagnóstico por imagem , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Ultrassonografia/métodos , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Sensibilidade e Especificidade
15.
Biochem Pharmacol ; 171: 113728, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759978

RESUMO

The multikinase inhibitor sorafenib, and opening of voltage dependent anion channels (VDAC) by the erastin-like compound X1 promotes oxidative stress and mitochondrial dysfunction in hepatocarcinoma cells. Here, we hypothesized that X1 and sorafenib induce mitochondrial dysfunction by increasing reactive oxygen species (ROS) formation and activating c-Jun N-terminal kinases (JNKs), leading to translocation of activated JNK to mitochondria. Both X1 and sorafenib increased production of ROS and activated JNK. X1 and sorafenib caused a drop in mitochondrial membrane potential (ΔΨ), a readout of mitochondrial metabolism, after 60 min. Mitochondrial depolarization after X1 and sorafenib occurred in parallel with JNK activation, increased superoxide (O2•-) production, decreased basal and oligomycin sensitive respiration, and decreased maximal respiratory capacity. Increased production of O2•- after X1 or sorafenib was abrogated by JNK inhibition and antioxidants. S3QEL 2, a specific inhibitor of site IIIQo, at Complex III, prevented depolarization induced by X1. JNK inhibition by JNK inhibitors VIII and SP600125 also prevented mitochondrial depolarization. After X1, activated JNK translocated to mitochondria as assessed by proximity ligation assays. Tat-Sab KIM1, a peptide selectively preventing the binding of JNK to the outer mitochondrial membrane protein Sab, blocked the depolarization induced by X1 and sorafenib. X1 promoted cell death mostly by necroptosis that was partially prevented by JNK inhibition. These results indicate that JNK activation and translocation to mitochondria is a common mechanism of mitochondrial dysfunction induced by both VDAC opening and sorafenib.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mitocôndrias/metabolismo , Sorafenibe/farmacologia , Canais de Ânion Dependentes de Voltagem/metabolismo , Antracenos/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Células Hep G2 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
16.
Eur Rev Med Pharmacol Sci ; 23(3 Suppl): 135-143, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31389584

RESUMO

OBJECTIVE: To investigate the effect of astaxanthin on the neurological function of the middle cerebral artery occlusion (MCAO) mice and its possible mechanism. MATERIALS AND METHODS: The male C57BL/6 mice were selected to establish the model of MCAO via electrocoagulation, and they were randomly divided into 4 groups: the sham operation group (Sham group), the cerebral ischemia model group (MCAO group), the astaxanthin intervention group (gavage with 30 mg/kg astaxanthin for 28 days, twice a day; Ast group), and astaxanthin + H89 group (Ast + H89 group). At 3, 7, 14, and 28 d after the operation, the Rotarod test and the balance beam footstep error test were performed. The brain tissues were taken for immunofluorescence to observe the expression of the growth-associated protein 43 (GAP43) in the cortex around the infarction. The GAP43 protein and mRNA levels in the cortex around the infarction were detected via Western blotting, and the Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the bilateral cerebral cortex were detected via enzyme-linked immunosorbent assay (ELISA), and the PKAc and phosphorylated-cAMP-response element-binding protein (p-CREB) levels in the bilateral cerebral cortex were detected via Western blotting. Biotin dextran amine (BDA) was injected at 14 d after the operation, and the brain was taken at 28 d. The BDA-labeled neurons or axons were observed in the bilateral cortex via immunohistochemistry and immunofluorescence, and the colocalization of BDA and GAP43 in the cortex around the infarction was observed using double immunofluorescence staining. RESULTS: Compared with those in the MCAO group, the mean residence time in the Rotarod test was significantly increased, and the times of the footstep error on the balance beam were significantly reduced in the Ast group. In the Ast group, the expression of GAP43 in the cortex around the infarction, the GAP43 protein, and the mRNA levels were all significantly elevated. Immunofluorescence showed that in the Ast group, the number of the labeled neurons and axons in the bilateral cortex was slightly larger than that in the other groups, and the number of labeled axonal fibers in the ischemic cortex was significantly increased. The colocalization area of BDA and GAP43 was observed, and it was found that the positive area in the Ast group was significantly larger than that in the MCAO group. The cAMP level was higher in the Ast group and Ast + H89 group at 7, 14, and 28 d after operation, while the PKA level was lower in the Ast + H89 group at 7 and 14 d after operation and higher in the Ast group at 7, 14, and 28 d after operation. The results of the Western blotting manifested that the PKAc and p-CREB levels were upregulated in the Ast group at 7, 14, and 28 d after the operation, and downregulated in the Ast + H89 group at 7, 14, and 28 d after the operation. CONCLUSIONS: Astaxanthin activates the cAMP/PKA/CREB signaling pathway by increasing the cAMP concentration in brain tissues, ultimately promoting the axonal regeneration in the cerebral cortex and improving the motor function.


Assuntos
Axônios/fisiologia , Infarto Cerebral/tratamento farmacológico , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Infarto Cerebral/metabolismo , Modelos Animais de Doenças , Esquema de Medicação , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração Nervosa/efeitos dos fármacos , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Xantofilas/administração & dosagem , Xantofilas/farmacologia
17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(2): 273-276, 2019 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-30996367

RESUMO

OBJECTIVE: To evaluate the association between rotator cuff tear and the proximal migration of humeral head. METHODS: In this research, we retrospectively selected 30 patients with unilateral rotator cuff tear in Peking University People's Hospital from September 2015 to May 2016, who received magnetic resonance imaging (MRI) and X-ray of the painful shoulder before enrollment in this study, the duration between the two examinations was no longer than 1 week, and also there was no past history of surgery in the selected shoulders. There was no other exclusion criteria. Upward migration index (UMI) was the ratio between the distance of humeral head center to the lower surface of acromion, and the radius of humeral head circle, which could help to minimize the effect of anatomy difference and imaging magnification, compared with the traditional acromiohumeral distance (AHD). Then we introduced this index to stratify the selected 30 patients into 3 groups, and each group contained 10 patients, UMI of group 1 was >1 and ≤1.2, UMI of group 2 was >1.2 and ≤1.4, UMI of group 3 was >1.4. As the supraspinatus was most commonly affected by pathological change among the four rotator cuff tendons, we took it as the research object. Then we used the Spearman correlation analysis to evaluate the relationship between UMI and fatty degeneration, rotator cuff tear size and the thickness of ruptured supraspinatus tendon from X-ray and MRI. RESULTS: In the A-P view, the average UMI was 1.33 (1.02-1.51, SD: ±0.22). UMI and the tear size had a significant negative correlation (R=-0.584, P<0.01), and also there was a negative correlation between the fatty degeneration of the supraspinatus (R=-0.312, P=0.033). However, there was no correlation between UMI and the thickness of ruptured supraspinatus (R=0.127, P=0.071). CONCLUSION: UMI is related with the fatty degeneration of supraspinatus and the tear size. The reduction of UMI is a predictable and reliable mark of rotator cuff tear and degeneration in clinic. Physicians can use physical examination and X-ray first when facing the patients with shoulder pain, which is convenient and helpful for evaluating rotator cuff tears.


Assuntos
Cabeça do Úmero , Lesões do Manguito Rotador , Articulação do Ombro , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Manguito Rotador
18.
Clin Radiol ; 74(4): 306-313, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30755314

RESUMO

AIM: To investigate the role of utilizing size-based thresholds of stiffness gradient in diagnosing solid breast lesions and optimizing original Breast Imaging-Reporting And Data System (BI-RADS) classifications. MATERIALS AND METHODS: Two-hundred and twenty-seven consecutive women underwent shear-wave elastography (SWE) before ultrasound-guided biopsy, and 234 solid breast lesions categorized as BI-RADS 3-5 were analysed. Receiver operating characteristic curve analysis was performed based on histopathology. Diagnostic performance among SWE, BI-RADS, and their combination were compared. RESULTS: The stiffness gradient correlated with the standard deviation of elasticity (SD, r=0.90), and with Tozaki's pattern classification (r=0.64). The area under the receiver operating characteristic curves (AUC) for stiffness gradient (0.939) outperformed SD (0.897) or colour pattern (0.852). Due to significant association with lesion size (r=0.394, p<0.001), stiffness gradient's size-based thresholds (lesions >15 mm: 82.5 kPa; lesions ≤15 mm: 51.1 kPa) were established to reclassify BI-RADS 3-4b lesions. Upgrading category 3 lesions (over the corresponding cut-off value, 3 to 4a) and downgrading categories 4a-4b lesions (less than or equal to the corresponding cut-off value, 4b to 4a, 4a to 3), yielded significant improvement in specificity (90.28% versus 77.78%, p<0.001) and AUC (0.948 versus 0.926, p=0.035) than BI-RADS alone. No significant loss emerged in the sensitivity (88.89% versus 91.11%, p=0.500). CONCLUSION: Stiffness gradient exhibited better discriminatory ability than SD or four-colour pattern classification in determining solid breast lesions and applying its size-specific thresholds to categorize BI-RADS 3-4b lesions could improve diagnostic performance.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Sistemas de Informação em Radiologia , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
19.
Fa Yi Xue Za Zhi ; 33(2): 175-180, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29231027

RESUMO

Forensic dentistry is an interdiscipline of forensic medicine and stomatology, which provides legal information by collecting, testing and assessing the dental evidence scientifically. In this review, the present application of forensic dentistry has been described, such as the estimation of age, sex, species, occupation and living habit, as well as the identification of individual, domestic violence or abuse, which aims to enrich and improve forensic dentistry for making it be more useful in forensic medicine even in juridical practice.


Assuntos
Determinação da Idade pelos Dentes , Odontologia Legal/métodos , Antropologia Forense , Medicina Legal , Humanos , Dente
20.
Zhonghua Jie He He Hu Xi Za Zhi ; 40(3): 182-187, 2017 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-28297812

RESUMO

Objective: To study the regulative effects of Aspergillus fumigatus (A.fumigatus) on expression of glucocorticoid receptor (GCR) in asthmatic rats. Methods: Wistar rats were randomly divided into 4 groups: a normal control group (UC), a normal control with A. fumigatus group (UC+ AF), an OVA group (OVA), and an OVA with A. fumigatus group (OVA+ AF). OVA and OVA+ AF groups were sensitized and challenged with OVA to establish asthmatic models. UC and UC+ AF groups were given normal saline as controls. After the last challenge, OVA+ AF and UC+ AF groups were given A. fumigatus spores intranasally. Airway hyper-responsiveness, eosinophil percentage (Eos%) and serum IgE level were measured to confirm the establishment of asthmatic models. Sections of pulmonary tissue were stained with hematoxylin-eosin (HE) and the expression of GCR mRNA and protein in lung tissues were measured by qRT-PCR and Western blot. Lung tissues and blood were plated on the potato dextrose agar(PDA)medium and cultured for 24 h to measure the number of colony. Results: The Penh value, Eos% in BALF and serum IgE level in UC+ AF group were slightly higher than those in the UC group (all the P>0.05). The Penh value, Eos% in BALF and serum IgE level in OVA group were significantly higher than those in the UC group (all the P<0.05). The Penh value in OVA+ AF group was significantly increased compared with the OVA group at the concentration of 25 g/L and 50 g/L of methacholine (all the P>0.05). Pulmonary histology revealed that both OVA group and OVA+ AF group showed high levels of inflammatory cell infiltration of bronchus and lung vessels, interstitial edema and smooth muscle thickening, while the UC and UC + AF groups were normal. Compared with the UC group, the expressions of GCR mRNA and protein in UC+ AF group and OVA group were decreased significantly (GCR mRNA in UC, UC+ AF and OVA group were 0.93±0.15, 0.65±0.10, 0.72±0.22, respectively, F=10.744, P<0.01; GCR protein in UC, UC+ AF and OVA group were 100±0, 89±8, 82±15, respectively, F=18.939, P<0.01). The expressions of GCR mRNA and protein in OVA+ AF group were further decreased than those in OVA group (GCR mRNA: OVA group: 0.72±0.22 vs OVA+ AF group: 0.52±0.08, t=2.462, P<0.05; GCR protein: OVA group: 81.88±15.41 vs OVA+ AF group: 59.09±7.60, t=2.997, P<0.05). The ratio of A. fumigatus colonization in lung tissues in OVA+ AF group (4/8) was higher than the UC+ AF group (0/8). Conclusion:A. fumigatus exposure can down-regulate the expression of GCR in the lung, which maybe an important mechanism of steroid-resistant asthma.


Assuntos
Aspergillus fumigatus , Asma/metabolismo , Pulmão/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Brônquios , Líquido da Lavagem Broncoalveolar , Contagem de Leucócitos , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar
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